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Citations & Evidence

The rule is simple: if a clinical claim can't be cited, it doesn't go on screen. This page collects the primary and authoritative sources behind the factory's clinical reasoning. Citations are provided so an expert can verify each claim against the source — please confirm the exact reference edition/version for any downstream use.

Variant interpretation & genomics

  • ClinVar — Landrum MJ, et al. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 2018. (clinical significance annotation)
  • ACMG/AMP variant classification — Richards S, et al. Standards and guidelines for the interpretation of sequence variants. Genet Med. 2015;17(5):405–424.
  • ACMG secondary-findings gene list — Miller DT, et al. ACMG SF v3.x list of genes for reporting of secondary findings in clinical exome/genome sequencing. Genet Med. 2023. (the E1 panel refresh)
  • AlphaMissense — Cheng J, et al. Accurate proteome-wide missense variant effect prediction with AlphaMissense. Science. 2023;381(6664):eadg7492. (missense pathogenicity prior)
  • Human Phenotype Ontology (HPO) — Köhler S, et al. The Human Phenotype Ontology in 2021. Nucleic Acids Res. 2021. (phenotype matching)
  • GIAB / HG002 — Zook JM, et al. Genome in a Bottle benchmark samples & truth sets. (the real data the variant store was verified against — Ts/Tv ≈ 2.0)

Single-cell

  • pbmc3k (10x Genomics) — the 3k-PBMC reference dataset, the canonical scanpy/Seurat tutorial data the single-cell compute engine was verified against: 2,700 cells → the expected PBMC cell types (CD4 T, B, NK, CD14+ & FCGR3A+ monocytes, dendritic, megakaryocytes) with correct marker-gene evidence.

Pharmacogenomics

  • CPIC — Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011; and the per-gene CPIC guidelines (cpicpgx.org). (the dosing/phenotype tables the Pharmacogenomics agent reasons over)

Oncology

  • CIViC — Griffith M, et al. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nat Genet. 2017. (therapy-actionability evidence)

Cardiology

  • ASCVD / Pooled Cohort Equations — Goff DC Jr, et al. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. Circulation. 2014;129(25 Suppl 2):S49–S73.
  • Coronary artery calcium (Agatston score) — Agatston AS, et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827–832.

Tuberous Sclerosis Complex (flagship)

  • Everolimus in TSC — Franz DN, et al. EXIST-1 (SEGA; Lancet 2013); Bissler JJ, et al. EXIST-2 (renal angiomyolipoma; Lancet 2013); French JA, et al. EXIST-3 (TSC-associated seizures; Lancet 2016). Everolimus is FDA-approved in TSC (SEGA 2010; renal AML 2012; adjunctive treatment of TSC-associated partial-onset seizures 2018).
  • Gene therapy for TSC1/TSC2 — preclinical. No approved gene therapy exists; the factory is an open design/analysis bench for this direction, not a treatment. See the Honesty & Governance ledger.

Note

Clinical outputs are decision support for a qualified clinician, never autonomous diagnosis or prescribing. Sources are cited to let experts check the work — the factory's job is to make the evidence legible and traceable, not to replace the clinician who weighs it.